Use of the bacteriophage-derived endolysin CHAPK-SH3blys as a potent novel treatment for biofilm-associated Staphylococcus aureus wound infections

The pathogenesis of Staphylococcus aureus acute and chronic wound infections is associated with biofilm formation. This study investigated the antimicrobial and antibiofilm potential of CHAPK-SH3blys, a bacteriophage-derived endolysin, against S. aureus strains implicated in chronic wound infections. CHAPK-SH3blys exhibited potent antibacterial activity with a minimum inhibitory concentration (MIC) of 3.9 µg/mL. Biofilm assays conducted under static and dynamic wound-like conditions showed a concentration-dependent reduction in biofilm metabolic activity, with up to a 4-log reduction in viable cells at concentrations 50 times the MIC. Further investigations revealed that CHAPK-SH3blys showed biocompatibility with human cell lines and did not induce an inflammatory response. Notably, prolonged exposure to sub-MIC levels did not lead to resistance development in S. aureus . These findings highlight CHAPK-SH3blys as a promising therapeutic agent for the treatment of biofilm-associated S. aureus wound infections. IMPORTANCE Successful treatment of wound infections, which is most commonly caused by the bacteria Staphylococcus aureus , is compromised by bacterial colonization resulting in slime layer or biofilm formation in the wound bed. Associated antimicrobial resistance (AMR) and limited treatment options can also impair wound healing and further highlight the need for the development and use of novel antimicrobial therapies. This study explores the antibiofilm and antimicrobial effectiveness of a bacteriophage-derived endolysin named CHAPK-SH3blys against S. aureus strains implicated in chronic wound infections. Bacteriophage-derived endolysin represents novel antimicrobial agents, and in this study, we demonstrate the effectiveness of this agent in treating wound and biofilm- related infections under wound-like conditions in the laboratory without affecting the immune response or inducing antimicrobial resistance. Due to the urgent public health need to develop alternative antimicrobial agents to combat biofilm-associated infections, our study highlights CHAPK-SH3blys as a promising and exciting candidate for further therapeutic development.